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Human plasminogen activator inhibitor-1 gene. Promoter and structural gene nucleotide sequences

Author: Bosma, P.J. · Berg, E.A. van den · Kooistra, T. · Siemieniak, D.R. · Slightom, J.L.
Type:article
Date:1988
Institution: Gaubius Institute TNO, 2313 AD Leiden, Netherlands
Source:Journal of Biological Chemistry, 19, 263, 9129-9141
Identifier: 230530
Keywords: Health · Plasminogen activator inhibitor · Dna sequence · Gene structure · Human · Human cell · Amino Acid Sequence · Base Sequence · Cloning, Molecular · Cosmids · Exons · Female · Genes, Structural · Glycoproteins · Human · Introns · Molecular Sequence Data · Placenta · Plasminogen Activators · Plasminogen Inactivators · Pregnancy · Promoter Regions (Genetics)

Abstract

We have determined the nucleotide sequence of the human plasminogen activator inhibitor-1 (PAI-1) gene and significant stretches of DNA which extend into its 5'- and 3'-flanking DNA regions; a total sequence of 15,867 base pairs (bp) is presented. The sequenced 5'-flanking DNA (1,520 bp) contains the essential eukaryotic cis-type proximal regulatory elements CCAAT and TATAA; the more distal 5'-flanking DNA region, as well as some introns, contain sequence elements which share identities with known eukaryotic enhancer elements. A major finding is the identification of a large region of shared nucleotides (comprising of about 520 bp) between the 5'-flanking DNAs of PAI-1 and tissue-type plasminogen activator genes. The length of the PAI-1 5'-untranslated region was found to be 145 bp as determined by nuclease analysis. The remaining PAI-1 structural gene consists of amino acid coding regions (containing a total of 1,206 bp, coding for the 23 amino acids of the signal peptide and 379 amino acids of the mature PAI-1 protein), 8 intron regions (a total of 8,978 bp), and a long 3'-untranslated region of about 1,800 bp which contains several polyadenylation sites. Two types of repetitive DNA elements are located within the PAI-1 structural gene and flanking DNAs: we have found 12 Alu elements and 5 repeats of a long poly (Pur) element. These Alu-Pur elements may represent a subset of the more abundant Alu family of repetitive sequence elements. Molecular Sequence Numbers: GENBANK: J03764; Chemicals/CAS: plasminogen activator inhibitor, 105844-41-5; Cosmids; Glycoproteins; Plasminogen Activators, EC 3.4.21.-; Plasminogen Inactivators